Hayri Özsan

A reappraisal of Gaucher disease-diagnosis and disease management algorithms.

Type 1 (non-neuronopathic) Gaucher disease was the first lysosomal storage disorder for which an effective enzyme replacement therapy was developed and it has become a prototype for treatments for related orphan diseases. There are currently four treatment options available to patients with Gaucher disease, nevertheless, almost 25% of Type 1 Gaucher patients do not gain timely access to therapy because of delays in diagnosis after the onset of symptoms. Diagnosis of Gaucher disease by enzyme testing is unequivocal, but the rarity of the disease and nonspecific and heterogeneous nature of Gaucher disease symptoms may impede consideration of this disease in the differential diagnosis. To help promote timely diagnosis and optimal management of the protean presentations of Gaucher disease, a consensus meeting was convened to develop algorithms for diagnosis and disease management for Gaucher disease.

The clinical, haematological and morphological profile of patients with myelodysplastic syndromes : A single institution experience from Turkey

In a retrospective analysis of 113 patients with primary myelodysplastic syndromes (MDS) diagnosed according to French-American-British (FAB) classification, we evaluated the prognostic impact of FAB and World Health Organisation (WHO) classifications, International Prognostic Scoring System (IPSS), and other clinical and laboratory variables. The median age was 69. IPSS could be applied to 75 patients classified according to the FAB criteria and to 50 patients reclassified according to the WHO criteria. At a median follow-up of 24 months, 22 patients (19.5 %) transformed to acute myelogenous leukaemia (AML). Overall survival (OS) of patients differed significantly between the FAB and WHO subgroups (p < 0.0001). In WHO classification, significant differences were observed in both OS and leukaemia free survival (LFS) between patients with RA/RARS and refractory cytopenia with multi-lineage dysplasia/refractory cytopenia with multi-lineage dysplasia and ringed sideroblasts (RCMD/RS-RCMD) (p = 0.0001). High-risk according to IPSS score and blood transfusion need were significantly predictive for a shorter survival and higher risk of transformation. Hemoglobin <10 g/dl, neutrophil count <0.5 × 109/L, platelet count <50 × 109/L had an unfavourable prognostic impact on survival in multi-variate analysis. Our conclusions support the previous findings on the value of WHO classification for prediction of prognosis in MDS.

Increased concentration of soluble CD40 ligand in preeclampsia.

Preeclampsia has been associated with increased platelet activation detected before disease onset. Platelets are involved in hemostasis and also directly initiate an inflammatory response of the vessel wall. Inappropriate activation of platelets may be involved in pathogenesis in preeclampsia by promoting coagulation and thrombosis, and also as a mediator of inflammation. Platelets may release inflammatory mediators such as soluble CD40 ligand. The plasma level of soluble CD40 ligand was investigated during preeclamptic (n =20) and normal pregnancies (n = 20) to emphasize inflammatory response in preeclampsia. The mean soluble CD40 ligand levels were 1.08 ± 0.43 ng/mL in patients with preeclampsia and 0.76 ± 0.24 ng/mL in healthy pregnant women, which was statistically significant (P = .01). To clarify whether inflammation may cause inappropriate endothelial cell activation or inappropriate endothelial cell activation may start this inflammatory response, future studies are needed in a larger study population.

Bilateral breast involvement in Sézary syndrome

Cutaneous T-cell lymphoma is a term used for mycosis fungoides and Sézary syndrome, the distinct clinical entities where the skin is the primary organ of involvement. Sézary syndrome is the leukemic variant of mycosis fungoides, presenting with generalized erythroderma, lymphadenopathy, and atypical cells (the Sézary cells) in the peripheral blood and bone marrow. The dissemination of cutaneous T-cell lymphoma may occur with no exception of the organs; however, no prior report exists about the Sézary syndrome secondarily involving the breasts. We report the clinical and radiological findings of bilateral breast involvement in a case of Sézary syndrome.

First observation of hemoglobin Crete [Beta129(H7) Ala>Pro] in the Turkish population.

Hemoglobin (Hb) Crete [β129 (H7) Ala>Pro] is a rare hemoglobin variant that was first reported in a Greek family living in USA, and then from Greece [1-4]. It was reported in combination with beta thalassemia and delta-beta-thalassemia [2], and also in a homozygous state [4]; however, this is the first report of Hb Crete in the Turkish population [5,6]. Herein we describe a 50-year-old Turkish man living in Izmir with Hb Crete. His family emigrated from Crete, Greece when he was 4 years old. He presented to the hospital with weight loss and hepatosplenomegaly. His routine hematological analysis results are shown in the Table 1. HPLC chromatography showed 1 abnormal band with 56.9% variance. Thoracoabdominal tomography showed hepatosplenomegaly and several multiple nodular lesions. Following posterolateral thoracotomy and paravertebral nodular excision, the histopathological diagnosis of the nodules was extramedullary hematopoiesis. Subsequently, the patient underwent splenectomy. We have the informed consent of the patient. PCR amplification of the β-globin gene was performed using primers F:5’-GGTT GGCCAATCTACT CCCAGGAG-3’ and R:5’-GCTCACTCAGTGTGGCAA AG-3’ for exon 1-exon 2. For exon 3, PCR amplification was performed first with the primers F:5’CAATGTATCATGCCTCTTTGCACC-3’ and R:5’GAGTCAAGGCTGA GAG ATAC AGGA-3’ for a 861bp fragment, and then 5’-TGCATATAAAT TGTAACTGAT-3’ and 5’-CACT GACCTCCCACAT TCCC-3’ primers were used for nested amplification. Direct automated sequencing of the all amplified regions of the β-globin gene was performed using an automatic sequencer (Beckmann Coulter, USA), and 2 different sets of PCR reactions with forward and reverse amplification were performed. The third exon amplification showed the variant as a missense mutation at codon 129 G change to C that leads to alanine substitution to proline, which was previously described as Hb Crete (Figure 1). Moreover, β-globin 5’ UTR + 20 (C-T) change was observed, indicating a combination with beta thalassemia. There are several reported 5’ UTR mutations of the β-globin gene that cause the β-thalassemia

Use of Tunnelled Catheters in Haematological Malignancy Patients with Neutropenia

This prospective study analysed 83 patients (age 45 ± 17 years) with haematological neoplasms, implanted with 93 tunnelled catheters, who were neutropenic or developed neutropenia during treatment. Catheters were implanted in the right (n = 82) or left (n = 11) jugular vein by the same surgical team using the same technique. They remained in place for 124 ± 88 days: 29% were removed due to infection; 18% due to treatment termination and 2% due to mechanical problems. Seventeen patients died with catheters in place. At 30, 60, 90, 120 and 200 days mean catheter duration rates were 82%, 75%, 65%, 60% and 35%, respectively, and freedom from catheter removal due to infection was 92%, 88%, 80%, 77% and 67%, respectively. Patient diagnosis and history of previous catheter infection did not increase catheter infection risk, but patients undergoing stem cell transplantation had an increased infection risk. Tunnelled catheters can be used in high-risk patients with neutropenia. Systemic infections can be managed in most patients without catheter removal.

High Lactoferrin Levels in Disseminated Intravascular Coagulation and Its Possible Negative Role in Coagulation

brile neutropenia standing of the role of factors affecting the pathogenesis may enable the individualization of the treatment. In the present study, plasma lactoferrin Lactoferrin (Lf), which shares a great deal of levels and neutrophil activation were assessed in homology with transferrin, is an iron-bindpatients with DIC, and the results were compared ing protein with a molecular weight of 80 with those of the healthy volunteers and those of kDa [1,2]. The main source of plasma lactoferrin the patients with leukomoid reaction (LR) as well is neutrophils, in which it is stored in specific granas in patients with febrile neutropenia (FN). ules [3]. Plasma lactoferrin is a reliable parameter reflecting total neutrophilic pool [4,5]. Lactoferrin plays a role in the defense against bacteria and 1. Materials and Methods regulation of the hematopoiesis and etiopathogenesis of anemia during the course of some diseases The study enrolled 14 patients with DIC (6 of which [6–9]. Since lactoferrin is an effective inhibitor of were secondary to malignancy and 8 of which were heparin-dependent anticoagulant activity, it is secondary to infection), 11 patients with LR, 18 claimed that lactoferrin may play a role in the patients with FN who were hospitalized at Dokuz pathogenesis of disseminated intravascular coaguEylul University Hospital, and 10 healthy volunlation (DIC) and thrombotic complications octeers. Peripheral venous blood samples were drawn curring during the course of inflammatory diseases into tubes containing EDTA, centrifuged within 1 [9]. DIC is a clinical entity characterized by unconhour, and plasma samples stored at 2708C. Comtrolled thrombin generation in systemic circulation plete blood counts with differential were obtained and by disseminated fibrin deposition in microcirin all patients. culation and bleeding diathesis. Complexity of the pathogenesis of DIC prevents the standardization 1.1. Plasma Lf Level Measurement

The Effect of Autologous Platelet Rich Plasma in the Treatment of Achilles Tendon Ruptures: An Experimental Study on Rabbits

BACKGROUND Achilles tendon ruptures are characterized by a long recovery period, high re-rupture rate and late return to work. To overcome these difficulties and augment tendon repair, many agents have been used. AIMS To determine the effect of autologous platelet rich plasma (PRP) in the treatment of Achilles tendon ruptures in rabbits. STUDY DESIGN Animal experimentation. METHODS The study included 14 New Zealand albino rabbits that were divided randomly into 2 groups, A and B, each containing seven rabbits. On day zero, all 28 Achilles tendons were tenotomized and repaired. In group A, the tendons were injected with PRP post-surgery, whereas those in group B were left untreated. On day 28, the right tendons in both groups were examined histopathologically via both light and electron microscopy, and the left tendons were subjected to biomechanical testing. RESULTS The histological and biomechanical findings in both light and electron microscopy in group A were better than those in group B, but the difference was not significant. According to Tangs scale, the mean value in Group A was 3.57, while it was 3.0 in Group B. The mean value of Group A for the length of collagen bands was 48.09 nm while the mean value of Group B was 46.58 nm (p=0.406). In biomechanical tests, although stiffness values were higher in group A, the difference between groups was not significant. In addition, maximum load values did not differ between groups A and B. CONCLUSION PRP had no effect on the healing process 28 days post-Achilles tendon rupture.

The Effect of FcγRIIIA Gene Polymorphism on the Treatment of Diffuse Large B-cell Non-Hodgkin Lymphoma: A Multicenter Prospective Observational Study

Objective: The curative treatment approach for diffuse large B-cell lymphoma (DLBCL) is controversial even in the rituximab (R) era. The aim of this study was to examine the FcγRIIIA gene polymorphism distribution of DLBCL patients who had been treated with R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Furthermore, we investigated the impact of FcγRIIIA gene polymorphism on the overall response rate (ORR) and overall survival (OS). Materials and Methods: Patients from 3 centers in the Aegean region of Turkey who had newly diagnosed CD20-positive DLBCL were enrolled in the study. The single nucleotide polymorphisms of the FcγRIIIA gene were analyzed by real time-PCR. The response to treatment was determined in the middle and at the end of the protocol. During 2 years of follow-up, the patients were clinically and radiologically evaluated for disease status every 3 months. Results: Thirty-six patients were included in the study and the distributions of F/F, V/F, and V/V types of alleles of FcγRIIIA were 25%, 50%, and 25%, respectively. Twenty-seven patients were considered as evaluable according to ORR and OS. The patients’ ORR was 87.5%, 100%, and 50% in the F/F, V/F, and V/V allele groups, respectively. We did not establish any statistically significant differences among the 3 alleles groups in respect to ORR (p=0.93). The OS within 2 years in the F/F, V/F, and V/V allele groups was 62.5%, 100%, and 100%, respectively. The OS in the F/F allele group was found to be lower than in the other 2 allele groups (p=0.01). Conclusion: The distribution of gene polymorphisms in our study group was similar to those of previous studies. While ORR was similar between the groups, our results highlight a lower OS in F/F patients compared to other allele groups of FcγRIIIA.

Does Reinfusion of Stem Cell Products on Multiple Days Affect Engraftment

Objective: High-doses of melphalan treatment with autologous stem cell transplantation in multiple myeloma (MM) remains a major treatment modality in suitable patients. A minimal dose of 2x106/kg CD34+ cells is preferred to achieve engraftment. Some patients need multiple leukapheresis procedures to achieve the necessary number of CD34+ cells, but this can cause a high volume of stem cell product that cannot be given in a single day. Whether or not the number of infusion days affects engraftment has not been studied before. We aimed to evaluate the impact of reinfusion of stem cells on multiple days on engraftment results. Materials and Methods: Demographic features, CD34+ cell doses, neutrophil and platelet engraftment days, hospitalization days, and number of infusion days of 149 autologous transplantations of 143 MM patients were evaluated retrospectively. Results: The data of 143 MM patients who were transplanted were analyzed retrospectively. Median age was 55±8.5 (range: 26-70) years with a male/female ratio of 91/58. Hospitalization days for all patients were 24±6 (range: 14-50) days. Mean CD34+ cell number was (7.5±5.3)x106/kg (range: 1.5-31x106/kg). CD34+ cells were reinfused in 1 day in 80.5% (n=120) of the patients, 2 days in 18.2% of the patients (n=27), and 3 days in 1.3% of the patients (n=2). For 29 patients, reinfusion was applied in more than 1 day because of the high volume of stem cell product. We did not see any dimethyl sulfoxide toxicity, cardiac arrhythmia, or volume overload complications. Hypertensive attacks during infusion were easily controlled by furosemide treatment. In the group with multiple infusions, the infused CD34+ cell numbers had a mean of (4.8±2.8)x106/kg, and in the single infusion group the mean was (8.1±5.5)x106/kg. There were no statistical differences between the two groups regarding platelet and neutrophil engraftment days (p=0.850, r=0.820 and p=0.500, r=0.440). There was no statistical difference between the two groups for hospitalization days (p=0.060, r=0.050). Conclusion: In cases with a high volume of stem cell product to acquire adequate stem cells, reinfusion can be safely applied across multiple days without any delay in engraftment.